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Eicosanoids comprise a diverse group of bioactive lipids which orchestrate inflammation, immunity, and tissue homeostasis, and whose dysregulation has been implicated in carcinogenesis. Among the various eicosanoid metabolic pathways, studies of their role in endometrial cancer (EC) have very much been confined to the COX-2 pathway. This study aimed to determine changes in epithelial eicosanoid metabolic gene expression in endometrial carcinogenesis; to integrate these with eicosanoid profiles in matched clinical specimens; and, finally, to investigate the prognostic value of candidate eicosanoid metabolic enzymes. Eicosanoids and related mediators were profiled using liquid chromatography-tandem mass spectrometry in fresh frozen normal, hyperplastic, and cancerous (types I and II) endometrial specimens (n = 192). Sample-matched epithelia were isolated by laser capture microdissection and whole genome expression analysis was performed using microarrays. Integration of eicosanoid and gene expression data showed that the accepted paradigm of increased COX-2-mediated prostaglandin production does not apply in EC carcinogenesis. Instead, there was evidence for decreased PGE

Specific antibodies against the C-terminus of E2, produced by affinity purification of polyclonal antisera, have been used to identify the cellular populations which express the HPV 16 E2 transcription factor, in a series of formalin-fixed, paraffin-embedded cervical tissues. Cases were selected for both the presence of HPV 16 DNA (confirmed by multiple gene-specific PCR detections) and the presence of multiple grades of cervical intraepithelial neoplasia (CIN). The data indicate that E2 expression is highest in CIN I and in koilocytic lesions. Lower expression was observed in CIN II and little in CIN III lesions. In contrast, there was some restoration of E2 expression in invasive carcinomas, although the intracellular distribution was much more diffuse. The location of E2 expression to the superficial layers of the cervical epithelium, as well as the occurrence of some basal expression in CIN I, suggests that antibodies against HPV 16 E2 could be a useful adjunct to standard histological techniques for the detection of 'at-risk' patients as part of a cervical screening programme.

The purpose of this study was to quantify vascular density in the stroma of normal, hyperplastic, and neoplastic endometria and to explore its relationship to other prognostic features of endometrioid adenocarcinoma. Curettage specimens of proliferative and mid-secretory endometrium; simple, complex, and atypical endometrial hyperplasia; and grade I endometrioid adenocarcinoma were stained with Factor VIII-related antigen. The number of vessels per mm2 of stroma was calculated for each case. The stroma of mid-secretory and hyperplastic endometrium was more vascular than that of proliferative endometrium. The stroma of adenocarcinoma, though reduced in proportion to the epithelium, was significantly more vascular than that of normal or hyperplastic endometrium. Stromal vascular density was not related to the depth of invasion, the presence of lymphovascular space permeation, or the state of the adjacent endometrium, whether atrophic or hyperplastic.

The ras oncogenes encode for GTP binding and GTPase active proteins of relative molecular mass 21 000 (p21ras) which are involved in the transduction of stimuli for cell proliferation. There have been conflicting reports about the detection and significance of expression of p21ras protein in human breast disease as determined by immunohistochemistry. The antibody Y13-259, which detects a single protein of Mr 21 000, has been applied immunohistochemically to frozen sections of normal, benign proliferative breast, fibroadenomas, and carcinomas. Uniform staining of normal breast epithelium and myoepithelium was found, with occasional stronger staining in areas of epithelial hyperplasia in benign breast disease. Contrary to previous reports, decreased expression, usually heterogeneous, was found in half of the carcinomas examined. Thirty per cent of the carcinomas exhibited heterogeneous staining stronger than that of normal breast, interpreted as increased expression of p21ras protein. This did not relate to tumour grade or node status but showed a significant correlation with proliferation rate as determined by the monoclonal antibody Ki-67. This study confirms previous reports that p21ras protein expression is a feature of normal cells, and has identified increased expression in 30 per cent of tumours associated with higher proliferation rates, which is a lower incidence than previously claimed when a different antibody was employed.